Citations

AbstractBackgroundProdromal dementia with Lewy bodies (DLB) research criteria were recently published and further work is needed to characterize the neuropsychological profile and refine clinical criteria. We performed a meta‐analysis to compare the cognitive performance of mild cognitive impairment with Lewy bodies (MCI‐LB) groups to controls, MCI due to Alzheimer’s disease (MCI‐AD), and DLB.MethodFollowing PRISMA guidelines, we searched the literature for 1) English‐language studies on MCI‐LB; 2) published January 1990‐March 2023, 3) with ≥1 standardized cognitive measure; and 4) comparison data from controls, MCI‐AD, and/or DLB. Pooled means with 95% confidence intervals were calculated for demographics. Effect sizes were calculated for group comparisons on cognitive domains. Random effects meta‐analysis models were used for group comparisons.ResultThere were 3440 participants from 27 studies across 10 countries. Mean age did not differ between groups. The percentage of female subjects was lower in the MCI‐LB group than the MCI‐AD group. Mean years of education for the MCI‐LB group was lower than the controls, but similar to MCI‐AD and DLB groups (Table 1). Compared to controls, the MCI‐LB group had lower scores for the global screening, executive function, visuospatial, language, learning, and memory domains. Compared to MCI‐AD, MCI‐LB performed better on learning and delayed recall, but similarly across other domains. Compared to DLB, MCI‐LB had better scores for global screening, executive function, language, and delayed recall (Table 2). Recognition for MCI‐LB vs. MCI‐AD; visuospatial, learning, and recognition for MCI‐LB vs. DLB could not be assessed, as fewer than 3 studies reported this data.ConclusionCognitive measures can help differentiate MCI‐LB from controls and DLB. Neuropsychological measures of learning and memory may be required to discriminate MCI‐LB from MCI‐AD in clinical practice but global screening measure scores appear insufficient in this regard. High heterogeneity across MCI‐LB studies highlights the need for harmonized neuropsychological research protocols.

ImportanceFrontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.ObjectiveTo evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.Design, Setting, and ParticipantsIn this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)–based executive functioning tasks and an associative memory task 3 times over 2 weeks. Observational research participants were enrolled through 18 centers of a North American FTLD research consortium (ALLFTD) and were asked to complete the tests remotely using their own smartphones. Of 1163 eligible individuals (enrolled in parent studies), 360 were enrolled in the present study; 364 refused and 439 were excluded. Participants were divided into discovery (n = 258) and validation (n = 102) cohorts. Among 329 participants with data available on disease stage, 195 were asymptomatic or had preclinical FTLD (59.3%), 66 had prodromal FTLD (20.1%), and 68 had symptomatic FTLD (20.7%) with a range of clinical syndromes.ExposureParticipants completed standard in-clinic measures and remotely administered ALLFTD mobile app (app) smartphone tests.Main Outcomes and MeasuresInternal consistency, test-retest reliability, association of smartphone tests with criterion standard clinical measures, and diagnostic accuracy.ResultsIn the 360 participants (mean [SD] age, 54.0 [15.4] years; 209 [58.1%] women), smartphone tests showed moderate-to-excellent reliability (intraclass correlation coefficients, 0.77-0.95). Validity was supported by association of smartphones tests with disease severity (r range, 0.38-0.59), criterion-standard neuropsychological tests (r range, 0.40-0.66), and brain volume (standardized β range, 0.34-0.50). Smartphone tests accurately differentiated individuals with dementia from controls (area under the curve [AUC], 0.93 [95% CI, 0.90-0.96]) and were more sensitive to early symptoms (AUC, 0.82 [95% CI, 0.76-0.88]) than the Montreal Cognitive Assessment (AUC, 0.68 [95% CI, 0.59-0.78]) (z of comparison, −2.49 [95% CI, −0.19 to −0.02]; P = .01). Reliability and validity findings were highly similar in the discovery and validation cohorts. Preclinical participants who carried pathogenic variants performed significantly worse than noncarrier family controls on 3 app tasks (eg, 2-back β = −0.49 [95% CI, −0.72 to −0.25]; P < .001) but not a composite of traditional neuropsychological measures (β = −0.14 [95% CI, −0.42 to 0.14]; P = .32).Conclusions and RelevanceThe findings of this cohort study suggest that smartphones could offer a feasible, reliable, valid, and scalable solution for remote evaluations of FTLD and may improve early detection. Smartphone assessments should be considered as a complementary approach to traditional in-person trial designs. Future research should validate these results in diverse populations and evaluate the utility of these tests for longitudinal monitoring.

AbstractDespite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public‐health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public‐domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor.Highlights A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

AbstractIntroductionOperationalized research criteria for mild cognitive impairment with Lewy bodies (MCI‐LB) were published in 2020. The aim of this systematic review and meta‐analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI‐LB set out in the criteria.MethodsMEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI‐LB.ResultsFifty‐seven articles were included. The meta‐analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta‐iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers.DiscussionThe available evidence largely supports the current diagnostic criteria for MCI‐LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research.Highlights A meta‐analysis of the diagnostic features of MCI‐LB was carried out. The four core clinical features were more common in MCI‐LB than MCI‐AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI‐LB. More evidence is needed for the proposed biomarkers. FDG‐PET and quantitative EEG show promise as diagnostic biomarkers in MCI‐LB.

Introduction: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. Methods: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. Results: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. Discussion: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

ABSTRACTBackgroundCorticobasal degeneration (CBD) can present with various clinical phenotypes including Richardson's syndrome (RS). Although neuropathological examination can differentiate CBD and progressive supranuclear palsy (PSP) pathologies, no clinical or imaging findings can differentiate CBD from other pathologies when a patient presents with a variant type of CBD. As these various phenotypes are associated with non‐CBD pathologies, clinical diagnostic accuracy can be low for such patients.ObjectivesTo present clinical features of two cases with symptom progression in line with PSP‐RS, who were diagnosed with CBD based on neuropathological examination.MethodsBaseline, follow up examinations, and detailed neuropathological examinations of two CBD cases presenting and progressing in line with probable PSP‐RS are demonstrated.ResultsThe two cases clinically diagnosed as probable PSP‐RS were shown to have CBD upon neuropathological examination, which is the gold standard for diagnosis of both PSP and CBD.ConclusionsThese cases emphasize the importance of neuropathology for the definite diagnosis, and stress the need for distinctive markers to increase the reliability of clinical diagnosis before death.